A quantitative characterisation of phospholipid composition and biosynthesis in HeLa cells and nuclei

Nuclei from human cells, stripped of their nuclear envelope by non-ionic detergent, contain a pool of endonuclear phospholipid that is distinct from that of other cellular membranes (Hunt et al., 2001 A. Hunt, G. Clark, G. Attard and A. Postle, J. Biol. Chem. 276 (11) (2001), pp. 8492–8499. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (52)Hunt et al., 2001). The composition dynamics, organisation and role of this endonuclear phospholipid are currently unclear, although there is mounting evidence of its possible involvement in the regulation of nuclear processes such as transcription (Martelli et al., 2004).We have conducted a study that correlates the composition of endonuclear phospholipid to the DNA replication cycle. Using tandem electrospray ionisation mass spectrometry, the phospholipid content of cultured HeLa (human cervical carcinoma) cells and their isolated naked nuclei has been determined quantitatively, both in the presence and absence of cell-cycle blocking agents such as mimosine (Krude, 1999). By harvesting nuclei at different times during the blocking procedure, or after release of the block we were able to monitor the endonuclear phospholipid composition throughout the cell cycle.Preliminary results indicate that the endonuclear lipid pool is enriched in diacyglycerol (DAG) compared with exonuclear lipids. The endonuclear DAG is also found to be enriched in saturated species. The potential implications of these observations on the cell-cycle dependence of lipid biosynthesis and on apoptosis are discussed

An in vivo ratio control mechanism for phospholipid homeostasis: evidence from lipidomic studies

While it is widely accepted that the lipid composition of eukaryotic membranes is under homeostatic control, the mechanisms through which cells sense lipid composition are still the subject of debate. It has been postulated that membrane curvature elastic energy is the membrane property that is regulated by cells, and that lipid composition is maintained by a ratio control function derived from the concentrations of type II and type 0 lipids, weighted appropriately. We assess this proposal by seeking a signature of ratio control in quantified lipid composition data obtained by electrospray ionization mass spectrometry from over 40 independent asynchronous cell populations. Our approach revealed the existence of a universal 'pivot' lipid, which marks the boundary between type 0 lipids and type II lipids, and which is invariant between different cell types or cells grown under different conditions. The presence of such a pivot species is a distinctive signature of the operation in vivo, in human cell lines, of a control function that is consistent with the hypothesis that membrane elastic energy is homeostatically controlled

FVIII inhibitor development according to concentrate: Data from the EUHASS registry excluding overlap with other studies

PubMed ID: 26208036[No abstract available